Objective To observe the effects of Yinqin Qingfei Granules on oxidative injury in lung tissue of mice with mycoplasma pneumoniae infection;To explore the mechanism of the Keap1/Nrf2/HO-1 signaling pathway in it.Methods Totally 100 BALB/c mice were randomly divided into blank group,model group,Yinqin Qingfei group,Azithromycin group and combination group,with 20 mice in each group.Except for the blank group,the other groups of mice were used to establish mycoplasma pneumoniae pneumonia model through bacterial solution nasal drip,and the blank group was given the same amount of normal saline nasal drip for 3 days.After modeling,the drug groups were given corresponding drugs by gavage,the blank group and the model group were given the same amount of distilled water by gavage,and the materials were taken at 3 and 7 days after administration,respectively.HE staining was used to observe the morphology of lung tissue,ELISA was used to detect the contents of interleukin(IL)-1β and tumor necrosis factor(TNF)-α in serum,biochemical method was used to detect the contents of nitric oxide(NO),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in lung tissue,Western blot was used to detect the expressions of Kelch like ECH associated protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)protein in lung tissue.Results Compared with the blank group,the lungs of mice in the model group showed severe inflammatory changes on day 3 and 7,with alveolar fusion or disappearance,and lung consolidation,which were more severe on day 7;the contents of IL-1β and TNF-α in serum significantly increased(P<0.05),the contents of SOD and GSH in lung tissues significantly decreased(P<0.05),and the contents of MDA and NO significantly increased(P<0.05),the protein expression of Keap1 in lung tissues increased(P<0.05),and Nrf2 and HO-1 protein expressions decreased(P<0.05).Compared with the model group,the histopathological changes in lung tissue showed different degrees of improvement on day 3 and 7 of drug treatment in Yinqin Qingfei group,Azithromycin group and combination group groups,the serum contents of IL-1β and TNF-α were significantly decreased(P<0.05),the contents of SOD and GSH in lung tissue were significantly increased on day 7 of drug treatment(P<0.05),the contents of MDA and NO significantly decreased(P<0.05),the protein expression of Keap1 in lung tissue decreased on day 3 and 7 of drug treatment(P<0.05),and the protein expressions of Nrf2 and HO-1 increased(P<0.05).Conclusion Yinqin Qingfei Granules can regulate the level of inflammatory factors,reduce lung inflammation and oxidative damage of mice with mycoplasma pneumoniae infection.The mechanism may be related to down-regulating the expression of Keap1,up-regulating the expressions of Nrf2 and HO-1,reducing the contents of NO and MDA,improving the activities of SOD and GSH,and playing an antioxidant role.

Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.

Objective To observe the effects of Yinqin Qingfei Granules on oxidative injury in lung tissue of mice with mycoplasma pneumoniae infection;To explore the mechanism of the Keap1/Nrf2/HO-1 signaling pathway in it.Methods Totally 100 BALB/c mice were randomly divided into blank group,model group,Yinqin Qingfei group,Azithromycin group and combination group,with 20 mice in each group.Except for the blank group,the other groups of mice were used to establish mycoplasma pneumoniae pneumonia model through bacterial solution nasal drip,and the blank group was given the same amount of normal saline nasal drip for 3 days.After modeling,the drug groups were given corresponding drugs by gavage,the blank group and the model group were given the same amount of distilled water by gavage,and the materials were taken at 3 and 7 days after administration,respectively.HE staining was used to observe the morphology of lung tissue,ELISA was used to detect the contents of interleukin(IL)-1β and tumor necrosis factor(TNF)-α in serum,biochemical method was used to detect the contents of nitric oxide(NO),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH)in lung tissue,Western blot was used to detect the expressions of Kelch like ECH associated protein 1(Keap1),nuclear factor E2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)protein in lung tissue.Results Compared with the blank group,the lungs of mice in the model group showed severe inflammatory changes on day 3 and 7,with alveolar fusion or disappearance,and lung consolidation,which were more severe on day 7;the contents of IL-1β and TNF-α in serum significantly increased(P<0.05),the contents of SOD and GSH in lung tissues significantly decreased(P<0.05),and the contents of MDA and NO significantly increased(P<0.05),the protein expression of Keap1 in lung tissues increased(P<0.05),and Nrf2 and HO-1 protein expressions decreased(P<0.05).Compared with the model group,the histopathological changes in lung tissue showed different degrees of improvement on day 3 and 7 of drug treatment in Yinqin Qingfei group,Azithromycin group and combination group groups,the serum contents of IL-1β and TNF-α were significantly decreased(P<0.05),the contents of SOD and GSH in lung tissue were significantly increased on day 7 of drug treatment(P<0.05),the contents of MDA and NO significantly decreased(P<0.05),the protein expression of Keap1 in lung tissue decreased on day 3 and 7 of drug treatment(P<0.05),and the protein expressions of Nrf2 and HO-1 increased(P<0.05).Conclusion Yinqin Qingfei Granules can regulate the level of inflammatory factors,reduce lung inflammation and oxidative damage of mice with mycoplasma pneumoniae infection.The mechanism may be related to down-regulating the expression of Keap1,up-regulating the expressions of Nrf2 and HO-1,reducing the contents of NO and MDA,improving the activities of SOD and GSH,and playing an antioxidant role.

Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.

Background and purpose:Human epidermal growth factor receptor 2(HER2)serves as one of the paramount drivers of breast cancer metastasis,with roughly 20%-30%of breast cancer patients exhibiting high expression of HER2.The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells;however,the manner in which HER2 expression is modulated at the mRNA level remains ambiguous.Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2,and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported.This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression.Methods:In this study,a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells.RNA fluorescence in situ hybridization(FISH)was utilized to detect the subcellular localization of circ-0007766.The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance.Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro.The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments,and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured.Additionally,it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972.A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972.The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment.RIP detection was performed in MDA-MB-231 cells,and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).Western blot was used to detect the protein expressions.Results:Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells,with the preponderance being in the cytoplasm.The expression level of circ-0007766 was strikingly higher in breast cancer tissues than in para-cancerous tissues.The expression of circ-0007766 was significantly elevated in HER2-positive breast cancer samples compared with HER2-negative samples.The overexpression(knockdown)of circ-0007766 in HER2-negative breast cancer cells(in HER2-positive breast cancer cells)was capable of promoting(inhibiting)the migration and invasion of breast cancer cells.Circ-0007766 directly bound to miR-1972,which inhibited breast cancer cell migration and invasion,thereby forming an endogenous competitive RNA(ceRNA)regulatory network and impeding the downregulation of HER2 mRNA and protein expression mediated by miR-1972.Circ-0007766 could potentiate the inhibitory effect of miR-1972 on HER2-mediated breast cancer cell migration and invasion that was negatively regulated by miR-1972.CircRNAs sequestered miRNAs to function as ceRNAs,thereby regulating gene expression at both the transcriptional and translational levels.Finally,we discovered that the expressions of circ-0007766 and HER2 were positively correlated in breast cancer cell and tissue samples,while the expression levels of miR-1972 and HER2 were negatively correlated.Circ-0007766 could specifically target miR-1972 to hinder its regulatory effect on HER2 expression.Conclusion:This study discovers that circ-0007766 facilitates the migration and invasion of breast cancer cells via the miR-1972/HER2 signal axis,offering a novel biomarker and potential therapeutic target for patients with metastatic HER2-positive breast cancer.

Objective:To explore the clinical efficacy of a retrograde pubic ramus intramedullary nail (RPRIN) in the treatment of anterior pelvic ring fractures.Methods:A retrospective study was conducted to analyze the 14 patients with anterior pelvic ring fracture who had been treated and followed up at Department of Traumatic Surgery, Tongji Hospital From June 2020 to February 2021. There were 10 males and 4 females with an age of (44.8±12.5) years. By the AO/OTA classification for pelvic fractures, 5 cases were type 61-A, 4 cases 61-B, and 5 cases type 61-C; by the Nakatani classification, 1 case belonged to unilateral zone Ⅰ fracture, 5 cases to unilateral zone Ⅱ fracture, 2 cases to unilateral zone Ⅲ fracture, 3 cases to right zone Ⅱ and left zone Ⅲ fracture, 2 cases to zone Ⅲ fracture on both left and right sides, and 1 case to zone Ⅱ fracture on both sides. The time from injury to operation was (7.8±1.8) days. All the anterior pelvic ring fractures were fixated with a RPRIN. The time and fluoroscopic frequency for placement of every single RPRIN, quality of fracture reduction, and pelvic function and incidence of postoperative complications at the last follow-up were recorded.Results:A total of 18 RPRINs were placed in the 14 patients. For placement of each RPRIN, the time was (35.9±8.6) min, and the fluoroscopic frequency (22.8±1.9) times. No complications such as infection occurred at any surgical incision after RPRIN placement. According to the Matta scoring, the quality of postoperative fracture reduction was assessed as excellent in 7 cases, as good in 5 cases and as fair in 2 cases. The 14 patients were followed up for (18.1+1.5) months. Their X-ray and CT images of the pelvis at the last follow-up showed that the fractures healed well and the intramedullary nails were placed in the cortical bone of the anterior ring of the pelvis. According to the Majeed scoring at the last follow-up, the pelvic function was assessed as excellent in 10 cases, as good in 3 cases and as fair in 1 case. One patient reported discomfort during squatting 2 months after operation but the symptom improved 3 months later without any special treatment. No patient experienced such complications as displacement or slippage of RPRIN, or pain at the insertion site.Conclusion:RPRIN is effective in the treatment of anterior pelvic ring fractures, showing advantages of small surgical incision, limited intraoperative fluoroscopy and short operation time.

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.
Female ; Humans ; Papillomavirus Infections/diagnosis* ; Retrospective Studies ; Uterine Cervical Neoplasms/pathology* ; Prognosis ; Oncogene Proteins, Viral/genetics* ; Human Papillomavirus Viruses ; Adenocarcinoma/pathology* ; RNA, Messenger/genetics* ; Papillomaviridae/genetics* ; RNA, Viral/genetics*

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Lung Neoplasms/diagnosis* ; Retrospective Studies ; Autoantibodies ; Bayes Theorem ; Tumor Suppressor Protein p53 ; Carcinoembryonic Antigen ; Antigens, Neoplasm ; Biomarkers, Tumor ; Algorithms ; Pneumonia

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Lung Neoplasms/diagnosis* ; Retrospective Studies ; Autoantibodies ; Bayes Theorem ; Tumor Suppressor Protein p53 ; Carcinoembryonic Antigen ; Antigens, Neoplasm ; Biomarkers, Tumor ; Algorithms ; Pneumonia

Objective: Propionic acidemia is a rare inherited metabolic disorder caused by propionyl CoA carboxylase (PCC) deficiency. This study aims to analyze the clinical characteristics and gene variations of Chinese patients with propionic acidemia, and to explore the correlation between clinical phenotypes and genotypes. Methods: Single-center, retrospective and observational study. Seventy-eight patients of propionic acidemia (46 males and 32 females) from 20 provinces and autonomous regions were admitted from January 2007 to April 2022. Their age of initial diagnosis ranged from 7 days to 15 years. The clinical manifestations, biochemical and metabolic abnormalities, genetic variations, diagnosis, treatment and outcome were studied. Chi-Square test or Mann-Whitney U test were used for statistical analysis. Results: Among 78 cases, 6 (7.7%) were identified by newborn screening; 72 (92.3%) were clinically diagnosed after onset, and the age of onset was 2 hours after birth to 15 years old; 32 cases had early-onset disease and 40 cases had late-onset disease. The initial manifestations included lethargy, hypotonia, vomiting, feeding difficulties, developmental delay, epilepsy, and coma. Among the 74 cases who accepted gene analysis, 35 (47.3%) had PCCA variants and 39 (52.7%) had PCCB variants. A total of 39 PCCA variants and 32 PCCB variants were detected, among which c.2002G>A and c.229C>T in PCCA and c.838dupC and c.1087T>C in PCCB were the most common variants in this cohort. The variants c.1228C>T and c.1283C>T in PCCB may be related to early-onset type. The variants c.838dupC, c.1127G>T and c.1316A>G in PCCB, and c.2002G>A in PCCA may be related to late-onset disease. Six patients detected by newborn screening and treated at asymptomatic stage developed normal. The clinically diagnosed 72 cases had varied complications. 10 (12.8%) cases of them died. 62 patients improved after metabolic therapy by L-carnitine and diet. Six patients received liver transplantation because of recurrent metabolic crisis. Their clinical symptoms were markedly improved. Conclusion: The clinical manifestations of propionic acidemia are complex and lack of specificity. Newborn screening and high-risk screening are keys for early treatment and better outcome. The correlation between the genotype and phenotype of propionic acidemia is unclear, but certain variants may be associated with early-onset or late-onset propionic acidemia.
Carnitine ; Female ; Genotype ; Humans ; Male ; Methylmalonyl-CoA Decarboxylase/metabolism* ; Mutation ; Phenotype ; Propionic Acidemia/genetics* ; Retrospective Studies